The Association between Antenatal Antimicrobial Therapy and Autism

Background: Autism spectrum disorder is a complex neurodevelopmental disorder affecting ~1% of live born children. Maternal infection during pregnancy has been suggested to play a role in ASD susceptibility, but the association between administration of antimicrobial therapy (AT) during pregnancy to treat these infections and ASD has not been examined thoroughly.

Methods: We conducted a case-control study in a population of children who were born in Soroka University Medical Center (SUMC) between the years 2008-2016. Cases were children who were diagnosed with ASD at the Negev Autism Center. Controls were matched to cases in a 5:1 ratio based on age, sex and ethnic origin, and included children with no known diagnosis of ASD, or other psychiatric or genetic disorders. Clinical data about the cases and control were obtain from the computerized database of SUMC. Multivariate conditional logistic regression models were used to assess the odds ratio (OR) of various infections during pregnancy, their AT, and their interactions on the risk of ASD.

Results: More than half of the women in the study had an infection during pregnancy (cases=51.2% and controls=55.8%; p=0.08), with upper respiratory tract (39.0%) and urinary (22.7%) being the most prevalent infections. Similarly, 49.0% of cases and 55.1% of controls (p=0.02) were prescribed AT during pregnancy with Beta-Lactam (45.4%) being the most prevalent prescriptions. Interestingly, most infections and/or prescribed AT during pregnancy were associated with a protective OR of ASD. However, the majority of interactions between them (i.e. infection x AT) were significantly associated with 2-4 fold increased risk of ASD (OR range = 1.96-3.81; p<0.05).

Conclusions: Our findings indicate that only infections treated with AT during pregnancy contribute to ASD susceptibility of the fetus. Further research to dissect the precise molecular mechanisms underlying this association is warranted.

Keywords: Autism Spectrum Disorder, Antimicrobials, Antibiotics, Antenatal, Pregnancy, Infection